From research lab to bedside, scientists and doctors collaborate to conquer childhood diseases

During the last century, scientists at The University of Texas at Austin played a large role in eliminating the nutritional deficiency diseases that were devastating to children's development with discoveries of vitamins like B5 and B6 and folic acid.

Today, a multi-disciplinary group of university researchers from the College of Pharmacy and College of Natural Sciences is joining forces at a new pediatric research facility to make a similar impact on children's health challenges.

Some of the significant problems -- like childhood obesity -- are different, but the dedication to improving children's health is the same.

The university's Dell Pediatric Research Institute (DPRI) is a state-of-the-art medical research facility that will advance understanding of childhood diseases and disorders and help take pediatric care in Central Texas to a new level. It is on the site of the old Robert Mueller Airport next to the Dell Children's Medical Center.

Dedication of the institute is April 23. DPRI research areas will include cancer, genetics, nutritional science, drug development, neuroscience and other fields that will enable advances in areas including childhood obesity, cancer, diabetes, birth defects, brain injury, epilepsy and autism.

John DiGiovanni

DPRI is being created as a result of a $38 million challenge grant from the Michael and Susan Dell Foundation that was announced in 2006. Other support has come from the RGK Foundation, the Bank of America Foundation and the Topfer family, as well as a significant investment from The University of Texas at Austin.

One unique feature of DPRI is that the research is directly linked to treatment. University researchers will be collaborating with doctors and other practitioners from Dell Children's Medical Center to translate study findings into medical products, prevention programs and treatments for children.

Faculty members will be conducting several areas of research at DPRI. Some programs -- like studies on obesity, childhood cancers, the immune system and vaccine delivery systems -- have already started.

Obesity: Its Impact on Human Health and the Cancer Link

One of the greatest childhood health problems today is the high prevalence of obesity and obesity-related diseases, including coronary heart disease, diabetes, stroke, hypertension, gallbladder disease, chronic respiratory disease and many cancers, say university faculty members John DiGiovanni and Stephen Hursting.

They will study the impact of obesity on cancer development and progression, including obesity that occurs early in life.

"Obesity in children has risen dramatically in recent years, and the growing epidemic is alarming," said DiGiovanni, who joined the Colleges of Pharmacy and Natural Sciences in January. "Obesity in both adults and children increases the risk of cancer development as well as severity of the disease for a number of important cancers."

Stephen Hursting

Over the past 25 years, the number of Texas children and adolescents who are overweight or obese has more than quadrupled, with nearly 25 percent of elementary, middle school and high school students overweight, and another 20 percent at high risk of becoming overweight.

The epidemic is occurring in girls and boys, across all socioeconomic lines and among all racial and ethnic groups.

"While we have made important gains over the past 20 years with early detection and better treatments for many cancers, there is no doubt that our progress in reducing the suffering and death from cancer has been significantly slowed by the obesity epidemic," said Hursting, who is chairman of the Department of Nutritional Sciences and specializes in obesity-cancer research.

Cancer is a disease involving gene-environmental interactions and, therefore, understanding environmental influences as well as genetic factors is key to developing the most effective strategies for preventing cancer, said the researchers.

"Understanding the early cellular, biochemical and molecular changes that transform normal cells into cancer cells is essential if we are to eventually eradicate cancer as a major human disease," DiGiovanni said.

"Approximately 75 percent of overweight children will be obese adults," he said. "Given the rising number of overweight and obese kids in Texas, it is extremely important to develop effective ways for preventing obesity and obesity-related diseases in children and young adults."

Chris Jolly

Hursting hopes the work of their team, which also includes nutritional science faculty members Drs. Linda deGraffenried and Nomeli Nunez, will lead to new strategies for reducing cancer with a combination of diet, exercise and medicine that will target specific genes.

"Our goal is to identify targets for breaking the obesity-cancer connection," he said. "We recognize that not everyone can run five miles a day or have a drastic change in diet. But if we can identify those molecular targets that are important we can use that information to disrupt the link between cancer and obesity."

How the Immune System Changes How We Age

Dr. Chris Jolly, associate professor of nutritional sciences, is examining the influence of diet and aging on immune function with emphasis on changes in dietary fat and fat metabolism throughout life.

Ultimately, he hopes to develop dietary and pharmacological ways to delay or offset reduced immune function in elderly people.

"How does fat metabolism in the immune system change throughout life, and how does that impact your susceptibility to infection and cancer?" said Jolly. "Can we come up with dietary fat changes to improve immune function?"

Immune aging begins when we are children, Jolly pointed out.

Zhengrong (Rong) Cui

"What we do in childhood," he said, "may then set the immune program for how well we age -- whether we age well or not."

He is studying fish and flax seed oils that are enriched in omega-3 fatty acids. Foods such as fish, some plants and nut oils are sources of omega-3 fatty acids. Research has shown they reduce inflammation and may help lower risk of chronic diseases such as heart disease, cancer and arthritis.

Jolly's goal is to have an immuno-diagnostic section in his lab, where researchers can take dietary compounds (new supplements or herbs) and new pharmacologic agents to conduct screening protocols to test effects on the immune system.

Developing New Vaccine Delivery Systems

Dr. Zhengrong (Rong) Cui, who also recently joined the College of Pharmacy faculty, is developing a novel model for the delivery of vaccines through the skin. He believes that not only will this be less painful for children, but it also has the potential to deliver a more effective vaccine.

"Vaccines are extensively given to children to promote the development of immunity against infectious diseases, and any development of new vaccines and alternative, non-invasive routes of vaccination would be very beneficial," said Cui, an associate professor of pharmaceutics.

"The skin has evolved to protect not only by acting as a physical barrier, but also by its role in our powerful immune system," said Cui.

Janet Walkow

He also is working to develop nanoparticles and using them as delivery systems for vaccine antigens or small molecular anti-cancer chemicals.

"Cancer is not limited to adults," he said. "Our experimental tumor therapy has the potential to be translated into new treatment methods for children with cancer."

Aiding the Development of New Drugs

TherapeUTex, an interdisciplinary effort to aid the development of potential medications developed by university faculty, also will be at DPRI as well as a Good Laboratory Practices (GLP) studies lab.

"The GLP studies are the all-important preclinical studies that are performed on drugs prior to gaining Federal Drug Administration (FDA) approval to conduct human clinical trials," said Dr. Janet Walkow, director of the College of Pharmacy Drug Dynamics Institute.

GLP studies can cost up to several million dollars if contracted to an outside vendor, said Walkow.

"The new GLP labs," Walkow said, "will provide a cost-effective option for faculty to pursue GLP development of new drugs."

She and Dr. Carla Van Den Berg, also of the College of Pharmacy, are leading the development of these new facilities.

Carla Van Den Berg

TherapeUTex offers a wide range of preclinical services to help establish feasibility for candidate drug therapies to pursue formal, GLP preclinical evaluation, said Van Den Berg, an associate professor of pharmacology and toxicology.

It initially will focus on animal models in the areas of cancer and pulmonary diseases such as asthma and other inflammatory lung diseases. The facility also will aid data generation by processing and imaging tissue or cell samples.

"The work performed by TherapeUTex is based on the expertise of university faculty and its ability to build collaborations between academia, federally funded research, corporate grants and sponsored research," said Van Den Berg.

Her independent research lab also will be at DPRI. Van Den Berg's studies focus on breast cancer and mammary gland development occurring in utero or during puberty. She also studies the underlying mechanisms for how cancer cells travel through the body and other factors that influence tumor progression and metastasis.